TY - JOUR
T1 - Disease Association of Anti‒Carboxyethyl Lysine Autoantibodies in Hidradenitis Suppurativa
AU - Macchiarella, Giulio
AU - Cornacchione, Vanessa
AU - Cojean, Celine
AU - Riker, Julia
AU - Wang, Yichen
AU - Te, Helene
AU - Ceci, Melanie
AU - Gudjonsson, Johann E.
AU - Gaulis, Swann
AU - Goetschy, Jean François
AU - Wollschlegel, Audrey
AU - Gass, Stephanie K.
AU - Oetliker-Contin, Sofia
AU - Wettstein-Ling, Barbara
AU - Schaefer, Dirk J.
AU - Meschberger, Pascale
AU - de Roche, Roland
AU - Osinga, Rik
AU - Wieczorek, Grazyna
AU - Naumann, Ulrike
AU - Lehmann, Joachim C.U.
AU - Schubart, Anna
AU - Hofmann, Andreas
AU - Roth, Lukas
AU - Florencia, Edwin F.
AU - Loesche, Christian
AU - Traggiai, Elisabetta
AU - Avrameas, Alexandre
AU - Prens, Errol P.
AU - Röhn, Till A.
AU - Roediger, Ben
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2023/2
Y1 - 2023/2
N2 - Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurring suppurating lesions of the intertriginous areas, resulting in a substantial impact on patients’ QOL. HS pathogenesis remains poorly understood. An autoimmune component has been proposed, but disease-specific autoantibodies, autoantigens, or autoreactive T cells have yet to be described. In this study, we identify a high prevalence of IgM, IgG, and IgA antibodies directed against Nε-carboxyethyl lysine (CEL), a methylglyoxal-induced advanced glycation end-product, in the sera of patients with HS. Titers of anti-CEL IgG and IgA antibodies were highly elevated in HS compared with those in healthy controls and individuals with other inflammatory skin diseases. Strikingly, the majority of anti-CEL IgG was of the IgG2 subclass and correlated independently with both disease severity and duration. Both CEL and anti-CEL‒producing plasmablasts could be isolated directly from HS skin lesions, further confirming the disease relevance of this autoimmune response. Our data point to an aberration of the methylglyoxal pathway in HS and support an autoimmune axis in the pathogenesis of this debilitating disease.
AB - Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurring suppurating lesions of the intertriginous areas, resulting in a substantial impact on patients’ QOL. HS pathogenesis remains poorly understood. An autoimmune component has been proposed, but disease-specific autoantibodies, autoantigens, or autoreactive T cells have yet to be described. In this study, we identify a high prevalence of IgM, IgG, and IgA antibodies directed against Nε-carboxyethyl lysine (CEL), a methylglyoxal-induced advanced glycation end-product, in the sera of patients with HS. Titers of anti-CEL IgG and IgA antibodies were highly elevated in HS compared with those in healthy controls and individuals with other inflammatory skin diseases. Strikingly, the majority of anti-CEL IgG was of the IgG2 subclass and correlated independently with both disease severity and duration. Both CEL and anti-CEL‒producing plasmablasts could be isolated directly from HS skin lesions, further confirming the disease relevance of this autoimmune response. Our data point to an aberration of the methylglyoxal pathway in HS and support an autoimmune axis in the pathogenesis of this debilitating disease.
UR - http://www.scopus.com/inward/record.url?scp=85142722194&partnerID=8YFLogxK
U2 - 10.1016/j.jid.2022.08.051
DO - 10.1016/j.jid.2022.08.051
M3 - Article
C2 - 36116506
AN - SCOPUS:85142722194
SN - 0022-202X
VL - 143
SP - 273-283.e12
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 2
ER -